The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3
Open accessAbstract
The Hsc/Hsp70 co-chaperones of the BAG (Bcl-2-associated athanogene) protein family are modulators of protein quality control. We examined the specific roles of BAG1 and BAG3 in protein degradation during the aging process. We show that BAG1 and BAG3 regulate proteasomal and macroautophagic pathways, respectively, for the degradation of polyubiquitinated proteins. Moreover, using models of cellular aging, we find that a switch from BAG1 to BAG3 determines that aged cells use more intensively the macroautophagic system for turnover of polyubiquitinated proteins. This increased macroautophagic flux is regulated by BAG3 in concert with the ubiquitin-binding protein p62/SQSTM1. The BAG3/BAG1 ratio is also elevated in neurons during aging of the rodent brain, where, consistent with a higher macroautophagy activity, we find increased levels of the autophagosomal marker LC3-II as well as a higher cathepsin activity. We conclude that the BAG3-mediated recruitment of the macroautophagy pathway is an important adaptation of the protein quality control system to maintain protein homeostasis in the presence of an enhanced pro-oxidant and aggregation-prone milieu characteristic of aging.
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“Increasing data indicate a significant association between senescence and autophagy in various cell systems (Gerland et al. 2003; Gamerdinger et al. 2009; Sasaki et al. 2010; Capparelli et al. 2012; Dörr et al. 2013).”
From Cellular senescence and its effector programs (2014) · cites this paper as Gamerdinger et al. 2009
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“Gamerdinger et al. (2009) showed a gradual shift in the degradation pathway for polyubiquitinated proteins from the proteasome pathway to autophagy during replicative senescence in HDFs.”
From Cellular senescence and its effector programs (2014) · cites this paper as Gamerdinger et al. 2009
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Citations
Cites
Pfaffl, M. W. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.9.e36 · Cited by 7,377
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388
How to Interpret LC3 Immunoblotting
Mizushima, N., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4600 · Cited by 2,595 · cited 1×
“A well-established marker for autophagy is LC3-II, and the autophagic flux can be measured by monitoring LC3-II accumulation in the presence of lysosomal inhibitors (Mizushima and Yoshimori, 2007).”
BackgroundAdapting Proteostasis for Disease Intervention
Balch, W. E., Morimoto, R. I., Dillin, A., & Kelly, J. W. (2008) · Science · doi:10.1126/science.1141448 · Cited by 2,495
Impairment of the Ubiquitin-Proteasome System by Protein Aggregation
Bence, N., Sampat, R. M., & Kopito, R. R. (2001) · Science · doi:10.1126/science.292.5521.1552 · Cited by 2,209
The roles of intracellular protein-degradation pathways in neurodegeneration
Rubinsztein, D. C. (2006) · Nature · doi:10.1038/nature05291 · Cited by 1,625
Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in C. elegans
Meléndez, A., Tallóczy, Z., Seaman, M., Eskelinen, E.-L., Hall, D. H., & Levine, B. (2003) · Science · doi:10.1126/science.1087782 · Cited by 1,270
Folding of Newly Translated Proteins In Vivo: The Role of Molecular Chaperones
Frydman, J. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.603 · Cited by 1,184
Pathways of chaperone-mediated protein folding in the cytosol
Young, J. C., Agashe, V. R., Siegers, K., & Hartl, F. U. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1492 · Cited by 1,121
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Dynamic profiling of the aggresome processing pathwayPreprint
Ghosh, S., Wang, L., Heß, D., Iešmantavičius, V., Englinger, J., Cao, C., Matthias, G., Seebacher, J., & Matthias, P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.30.684516
“(e.g., BAG3, TUBB, HSPA1A, HSPA1B highlighted in bold black; Fig.3B, group 1 and 3).”
InfluentialRole of Autophagy in Post-Mitotic Midbody Fate and Function: A Dissertation
Kuo, T.-C. (2013) · eScholarship@UMassChan · doi:10.13028/m2mc75
Liver‐specific BAG3 knockout delays chemically induced hepatocellular carcinoma development
Damiani, V., Pizzinato, E., Marco, F. D., Lamolinara, A., Pizzo, F., Navicella, A., Dufrusine, B., Lanuti, P., Dainese, E., Lattanzio, R., et al. (2026) · FEBS Journal · doi:10.1111/febs.70381
“In particular, under acute stress and during cellular aging, BAG3 in concert with the ubiquitin receptor p62/SQSTM1 (hereafter referred to as p62) specifically targets aggregation-prone proteins to autophagic degradation [40].”
Zhu, G., Wang, S. C. Y., He, J., Zhang, J., Zhang, M., & Wang, Y. (2026) · Cancers · doi:10.3390/cancers18020243
“BAG3 facilitates cancer progression and maintains protein quality control during aging via macro-autophagy pathway recruitment [40,41].”
Perry, A., O’Connor, C. M., Pavicic, M., Sheng, Q., Farber‐Eger, E. H., Sarkar, A., Lin, P., Evans, P. D., Tanrıverdi, K., Risitano, A., et al. (2026) · medRxiv · doi:10.64898/2026.02.12.26346203
BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes
Rodwell‐Bullock, J., Blau, E., Ganguly, A., Deaton, C. A., & Johnson, G. V. W. (2026) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00947.2025
Rôle de la protéine BAT3 dans la signalisation cellulaire de l'autophagie
Sebti, S. (2013) · theses.fr (ABES) · doi:10.70675/31574cd0z6062z4118z8c09za6ba5861b645
Study of lymphocyte autophagy in normal and autoimmune responses
Murera, D. (2016) · theses.fr (ABES) · doi:10.70675/ab9d3ba4z5522z4d8aza5dbz681fe3fa1e44
Korniat, A. (2015) · theses.fr (ABES) · doi:10.70675/5e1e0f46zc795z457dz9339zf25c8995cb55
Autophagy in antigen presenting cells
Arbogast, F. (2018) · theses.fr (ABES) · doi:10.70675/34dc5979z744bz4dbcz8706z138eacecef37
Role of NALCN channel in prostate cancer metastatic behaviours
Iamshanova, O. (2017) · theses.fr (ABES) · doi:10.70675/17cbb427z4f8dz49b8z97a4zb37243113aac
Vaja, R., & Baxi, D. (2026) · Journal of Proteins and Proteomics · doi:10.1007/s42485-026-00209-y
“For instance, BAG1 links HSP70 to the proteasomal degradation pathway, whereas the BAG3-HSP70 complex plays a central role in regulating protein aggregation and quality control (Behl 2011; Gamerdinger et al. 2009).”
Liu, Y., Xia, G., Shi, H., Zhu, S., Li, H., Shi, Y., Ouyang, W. X., Xu, C., & Du, A. (2026) · Autophagy · doi:10.1080/15548627.2026.2693778
“As a specific form of aggrephagy, chaperone-assisted selective autophagy (CASA) recognizes substrates through an ATP-regulated transient association with exposed hydrophobic regions by CASA complex, including HSPA and the co-chaperones BAG3 and HSPB8 [25–27].”
Milardi, D., Han, J., Lee, H. J., Ding, F., Miller, Y., Faller, P., Bush, A. I., Crouch, P. J., Finkelstein, D. I., Double, K. L., et al. (2026) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00420
Quantitative proteomics reveals coordinated changes in the proteome during replicative senescence
Fernandes, N. D. S., Kielisch, F., Fulzele, A., Karunanithi, S., Gräf, J. F., Chen, J., Behl, C., Ulrich, H. D., & Beli, P. (2026) · Nature Communications · doi:10.1038/s41467-026-77686-8
Self-citationDjabali, K. (2026) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2026.112255
Augur, Z. M., Fogo, G. M., Benoit, C. R., Kearney, M., Terzioğlu, G., Murphy, Z. R., Arbery, M. R., Comandante-Lou, N., Duong, D. M., Seyfried, N. T., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2528514123 · Cited by 3
Ribosome structure, function and dysfunction at the molecular level
Chitale, R., & Johnson, A. M. (2026) · Seminars in Hematology · doi:10.1053/j.seminhematol.2026.09.011
Schaiter, A., Lohanadan, K., Mensch, A., Hentschel, A., Rosenbohm, A., Kornblum, C., Roth, A., Procida‐Kowalski, T., Krämer, H. H., Hahn, A., et al. (2026) · Brain Pathology · doi:10.1111/bpa.70155
“BAG3 is a key player in CASA [71 – 73].”
Research progress on the BAG3-HSP70 axis-mediated autophagy in acute myeloid leukemia
Liu, Y., & Wu, T. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1980188
“BAG1 preferentially routes HSP70 clients to the ubiquitin-proteasome system, whereas BAG3 recruits the autophagy-lysosomal pathway; during aging and under proteasome impairment the BAG3-to-BAG1 ratio rises and the macroautophagy arm becomes dominant (Gamerdinger et al., 2009).”
Metadata
- Authors
- Gamerdinger, M., Hajieva, P., Kaya, A. M., Wolfrum, U., Hartl, F. U., & Behl, C.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Behl, Christian
- Venue
- The EMBO Journal
- Published
- 2009-02-19
- Volume
- 28
- Issue
- 7
- Pages
- 889-901
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2647772
- OpenAlex
- W2094186182
- Cited by
- 522
- References
- 42
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 20 · 2023: 24 · 2022: 33 · 2021: 32 · 2020: 25 · 2019: 23 · 2018: 37 · 2017: 47 · 2016: 38 · 2015: 33 · 2014: 32 · 2013: 35 · 2012: 25
- FWCI
- 23.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- protein quality control, aging, BAG3, BAG-1, macroautophagy, autophagy, polyubiquitinated proteins, proteasome, p62, LC3-II, cathepsin activity, neuronal aging, brain aging, proteostasis, protein aggregation, oxidative stress
- MeSH terms
- Animals, Autophagy, DNA-Binding Proteins, Humans, Immunohistochemistry, Transcription Factors, Cellular Senescence, Rats, Sprague-Dawley, Microscopy, Electron, Transmission, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Mice, Rats
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